Dataset Information

HIV-1 Nef is associated with complex pulmonary vascular lesions in SHIV-nef-infected macaques.

ABSTRACT:

Rationale

HIV-infected patients with pulmonary arterial hypertension have histologic manifestations that are indistinguishable from those found in patients with idiopathic pulmonary arterial hypertension. In addition, the role of pleiotropic viral proteins in the development of plexiform lesions in HIV-related pulmonary hypertension (HRPH) has not been explored. Simian immunodeficiency virus (SIV) infection of macaques has been found to closely recapitulate many of the characteristic features of HIV infection, and thus hallmarks of pulmonary arterial hypertension should also be found in this nonhuman primate model of HIV.

Objectives

To determine whether pulmonary arterial lesions were present in archived SIV-infected macaque lung tissues from Johns Hopkins University and two National Primate Research Centers.

Methods

Archived macaque and human lung sections were examined via immunohistochemistry for evidence of complex vascular lesions.

Results

Complex plexiform-like lesions characterized by lumenal obliteration, intimal disruption, medial hypertrophy, thrombosis, and recanalized lumena were found exclusively in animals infected with SHIV-nef (a chimeric viral construct containing the HIV nef gene in an SIV backbone), but not in animals infected with SIV. The mass of cells in the lesions were factor VIII positive, and contained cells positive for muscle-specific and smooth muscle actins. Lung mononuclear cells were positive for HIV Nef, suggesting viral replication. Endothelial cells in both the SHIV-nef macaques and patients with HRPH, but not in patients with idiopathic pulmonary arterial hypertension, were also Nef positive.

Conclusions

The discovery of complex vascular lesions in SHIV-nef- but not SIV-infected animals, and the presence of Nef in the vascular cells of patients with HRPH, suggest that Nef plays a key role in the development of severe pulmonary arterial disease.

SUBMITTER: Marecki JC

PROVIDER: S-EPMC2648120 | biostudies-literature | 2006 Aug

REPOSITORIES: biostudies-literature

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Publications

HIV-1 Nef is associated with complex pulmonary vascular lesions in SHIV-nef-infected macaques.

Marecki John C JC Cool Carlyne D CD Parr Jane E JE Beckey Virginia E VE Luciw Paul A PA Tarantal Alice F AF Carville Angela A Shannon Richard P RP Cota-Gomez Adela A Tuder Rubin M RM Voelkel Norbert F NF Flores Sonia C SC

American journal of respiratory and critical care medicine 20060525 4

<h4>Rationale</h4>HIV-infected patients with pulmonary arterial hypertension have histologic manifestations that are indistinguishable from those found in patients with idiopathic pulmonary arterial hypertension. In addition, the role of pleiotropic viral proteins in the development of plexiform lesions in HIV-related pulmonary hypertension (HRPH) has not been explored. Simian immunodeficiency virus (SIV) infection of macaques has been found to closely recapitulate many of the characteristic fea ...[more]

PMID: 16728715

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Dataset Information

HIV-1 Nef is associated with complex pulmonary vascular lesions in SHIV-nef-infected macaques.

Rationale

Objectives

Methods

Results

Conclusions

Publications

HIV-1 Nef is associated with complex pulmonary vascular lesions in SHIV-nef-infected macaques.

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